There is a clinical need for a new cost-effective, non-toxic therapy to treat Respiratory Syncytial Virus (RSV) infections in young children and immunocompromised adults. Microbiotix, Inc. is developing NMSO3 as a treatment, intranasal delivery, for RSV infection. NMSO3 has been shown to be active in vitro (IC50 = 0.20mu/m) and in animals (Cotton Rat) against RSV infection (Kimura et al., 2000). We have extended those observations in our Phase I SBIR studies to confirm the anti-RSV activity and mechanism of action. We have also produced gram quantities of compound, establish pharmacokinetic parameters and developed analytical techniques for NMSO3 detection. Based upon our bioavailability studies, we found NMSO3 was not taken up well by the oral route. However, we have now shown that when given by the intranasal route, NMSO3 eliminates detectable virus in the lung of RSV infected cotton rats. We have also now established that based upon sequencing of NMSO3 resistant mutants NMSO3 appears to inhibit RSV infection by interfering with the viral G protein. We are unaware of any other compound in development as a anti-RSV agent with this mechanism of action. We have also shown that NMSO3 can inhibit chemokine (MCP-1, RANTES, IP-10) production, induced by RSV in lung airway epithelial cells. It is our aim in the Phase II SBIR to expand the preclinical profile of NMSO3 and move the compound into IND enabling pharmacokinetic, toxicology and safety pharmacology studies. We will refine the optimum dosing regimen for treating RSV lung infections in cotton rats. Coupled with the pharmacokinetic profile and toxicological studies we will then establish a safety index based upon plasma drug concentrations. GMP quality NMSO3 will be prepared. The goal is to file an Investigational New Drug Application (IND) for NMSO3 to treat RSV infection within two years of initiation of the Phase II SBIR studies. Furthermore, we have recently shown NMSO3 to be active against human Metapneumovirus (hMPV) in vitro. Human MPV, which is closely related to human RSV, is also a significant respiratory pathogen. Our plan going forward is to continue to investigate the anti-hMPV activity of NMSO3. Anti-hMPV activity can be examined as part of our clinical Phase II studies.